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Michael S Ewer

Publications and source records attributed to Michael S Ewer.

11 recordsLinked to original sources
PubMed2007

Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen.

PURPOSE: Findings from our previously published phase III randomized trial showed a high pathologic complete remission (CR) rate in patients with human epidermal growth factor receptor 2-positive breast cancer after the concurrent administration of trastuzumab and paclitaxel, followed by concurrent trastuzumab and 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) preoperative chemotherapy. The safety and efficacy data of initial population were updated, with inclusion of additional experience with the same therapy. STUDY DESIGN: The initial randomized study population of 42 patients were randomly assigned to either four cycles of paclitaxel followed by four cycles of FEC or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. All data were updated through November 2005. RESULTS: Pretreatment characteristics of the initial patients and of the second cohort were similar. In the second cohort, pathologic CR rate was 54.5% (95% confidence interval, 32.2-75.6%) and the pathologic CR rate among all patients treated with chemotherapy plus trastuzumab was 60% (95% confidence interval, 44.3-74.3%). Three patients in the chemotherapy only group have recurred, and one has died. There has been no recurrences in the patients randomized to chemotherapy plus trastuzumab, and the estimated disease-free survival at 1 and 3 years was 100% (P = 0.041). In additional cohort treated with chemotherapy and trastuzumab at the median follow-up of 16.3 months, no patients had recurred. No new safety concerns were observed in this study. CONCLUSION: Our expanded cardiac safety data and the updated efficacy data showed that the natural history of this subset of breast cancer patients can be substantially modified by this treatment approach.

Adult↗
PubMed2006

Anthracycline cardiotoxicity.

The use of anthracyclines is limited by dose-dependent cardiotoxicity. Three forms of anthracycline cardiotoxicity are described; an immediate pericarditis-myocarditis syndrome, an early onset chronic progressive CHF developing during or shortly after therapy and late-onset cardiotoxicity presenting years following treatment. A number of risk factors have been reported, including; cumulative dose, administration schedule, mediastinal radiotherapy, old and young age, concurrent cardiovascular disease, combination therapy, gender, ethnicity and chromosomal abnormalities. Evaluation of left ventricular ejection fraction has been widely adopted as a means of monitoring and assessing anthracycline-induced cardiotoxicity. Biochemical markers and other techniques, such as endomyocardial biopsy, metaiodobenzylguanidine and indium-111-antimyosin scintigraphy are not routinely used. Methods employed to prevent cardiotoxicity include cumulative dose limitation, alteration of administration schedule, anthracycline analogues, liposomal formulations and the cardioprotective agent, dexrazoxane. With the growing number of paediatric malignancy survivors and the increasing use of anthracyclines in the adjuvant treatment of breast cancer, the cardiotoxicity associated with these agents will remain a formidable issue for physicians. Further work is required to identify patients at increased risk of cardiotoxicity and to develop novel methods of protecting and treating this adverse effect.

Anthracyclines↗
PubMed2006

Cardiac and cardiovascular toxicity of nonanthracycline anticancer drugs.

Anthracyclines are a well-known cause of cardiotoxicity, but a number of other drugs used to treat cancer can also result in cardiac and cardiovascular adverse effects. Cardiotoxicity can result in the alteration of cardiac rhythm, changes in blood pressure and ischemia, and can also alter the ability of the heart to contract and/or relax. The clinical spectrum of these toxicities can range from subclinical abnormalities to catastrophic life-threatening, and sometimes fatal, sequelae. These events may occur acutely or may only become apparent months or years following completion of oncological treatment. Ischemia and rhythm abnormalities are treated symptomatically in most cases. Knowledge of these toxicities can aid clinicians to choose the optimal and least toxic regimen suitable for an individual patient.

Anthracyclines↗
PubMed2005

Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment.

PURPOSE: Trastuzumab is an important biologic agent with significant activity in breast cancers that overexpress the HER2/neu marker. However, trastuzumab is associated with cardiotoxicity that has not yet been fully explored. We present our experience with patients who developed trastuzumab-related cardiotoxicity. PATIENTS AND METHODS: Over a 4-year period, 38 patients with HER2/neu-positive breast cancer were referred for suspected trastuzumab-related cardiotoxicity. All patients had previously received anthracycline-based chemotherapy. Results After doxorubicin but before trastuzumab, the mean (+/- standard deviation) left ventricular ejection fraction (LVEF) was 0.61 +/- 0.13, and the LVEF decreased to 0.43 +/- 0.16 after trastuzumab (P < .0001). After withdrawal of trastuzumab, the LVEF increased to 0.56 +/- 0.11. Mean time to recovery of LVEF was 1.5 months and was temporally associated with medical treatment in 32 (84%) of the 38 patients but occurred without treatment in six patients (16%). Increases in LVEF were noted in 37 of the 38 patients. Twenty-five of these patients were re-treated with trastuzumab; three patients had recurrent left ventricular dysfunction, but 22 patients (88%) did not. All re-treatment patients continued on their therapeutic regimen for heart failure when rechallenged with trastuzumab. Nine patients underwent endomyocardial biopsy. Ultrastructural changes were not seen. CONCLUSION: Patients who develop cardiotoxicity while receiving trastuzumab therapy generally improve on removal of the agent. The mechanism of trastuzumab-related cardiac dysfunction is different from that of anthracycline cardiotoxicity, in part, demonstrated by the absence of anthracycline-like ultrastructural changes. Reintroducing trastuzumab may be appropriate for some individuals who previously have experienced trastuzumab-related cardiac dysfunction.

Adult↗
PubMed2005

Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.

Adult↗
PubMed2004

Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management.

The cardiotoxicity of anticancer agents can lead to significant complications that can affect patients being treated for various malignancies. The severity of such toxicity depends on many factors such as the molecular site of action, the immediate and cumulative dose, the method of administration, the presence of any underlying cardiac condition, and the demographics of the patient. Moreover, toxicity can be affected by current or previous treatment with other antineoplastic agents. Cardiotoxic effects can occur immediately during administration of the drug, or they may not manifest themselves until months or years after the patient has been treated. In this article we review commonly used chemotherapy agents, including several recently approved medications, for their propensity to cause cardiotoxicity. Further research will be required to more accurately predict which patients are at risk for developing cardiotoxicity. In addition, management plans, as well as strategies to reduce cardiotoxicity, need to be developed.

Anthracyclines↗
PubMed2004

Cardiac safety of liposomal anthracyclines.

Conventional anthracyclines are active against many tumor types, but cardiotoxicity related to the cumulative dose may limit their use; this is particularly problematic for patients with risk factors for increased toxicity, for those who have received any anthracycline in the past, or for those who are to receive other cardiotoxic agents. Preclinical studies determined that encapsulating conventional anthracyclines in liposomes reduced the incidence and severity of cumulative dose-related cardiomyopathy while preserving antitumor activity. In controlled clinical trials, the risk of cardiotoxicity was significantly lower when nonpegylated liposomal doxorubicin (Myocet [NPLD]) was substituted for conventional doxorubicin, but the risk was not significantly different when NPLD was used in place of conventional epirubicin. Direct comparisons to conventional doxorubicin therapy showed comparable efficacy but significantly lower risk of cardiotoxicity with pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) therapy. Retrospective and prospective trials have not identified a maximum "cardiac safe" dose of PLD, despite use of cumulative doses exceeding 2,000 mg/m2 in some patients. Liposomal daunorubicin (DaunoXome [DNX]) may be associated with a lower risk of cardiotoxicity than conventional anthracyclines, but comparative trials are not available. With respect to combination chemotherapy, early results of clinical trials suggest that combining trastuzumab or a taxane with NPLD or PLD instead of a conventional anthracycline significantly reduces cardiotoxicity risk without reducing chemotherapeutic efficacy. Further results are eagerly awaited from ongoing controlled trials of cardiac safety with long-term liposomal anthracycline therapy, either alone or in combination with other potentially cardiotoxic agents.

Anthracyclines↗
PubMed2003

Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials.

BACKGROUND: Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug. A large-scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7% of patients developed doxorubicin-related congestive heart failure (CHF) after a cumulative dose of 550 mg/m(2). To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting, the authors evaluated data from three prospective studies to determine both the incidence of doxorubicin-related CHF and the accumulated dose of doxorubicin at which CHF occurs. METHODS: A group of 630 patients who were randomized to a doxorubicin-plus-placebo arm of three Phase III studies, two studies in patients with breast carcinoma and one study in patients with small cell lung carcinoma, were included in the analysis. RESULTS: Thirty-two of 630 patients had a diagnosis of CHF. Analysis indicated that an estimated cumulative 26% of patients would experience doxorubicin-related CHF at a cumulative dose of 550 mg/m(2). Age appeared to be an important risk factor for doxorubicin-related CHF after a cumulative dose of 400 mg/m(2), with older patients (age > 65 years) showing a greater incidence of CHF compared with younger patients (age < or = 65 years). In addition, > 50% of the patients who experienced doxorubicin-related CHF had a reduction < 30% in left ventricular ejection fraction (LVEF) while they were on study. CONCLUSIONS: Doxorubicin-related CHF occurs with greater frequency and at a lower cumulative dose than previously reported. These findings further indicate that LVEF is not an accurate predictor of CHF in patients who receive doxorubicin.

Adult↗
PubMed2002

Outcome and cost implications of cardiopulmonary resuscitation in the medical intensive care unit of a comprehensive cancer center.

Intensive care unit (ICU) resources are frequently utilized in the supportive care of hospitalized patients with cancer. Patients with cancer reportedly have poor outcomes from cardiopulmonary resuscitation (CPR). The goal of this study was to evaluate the effectiveness and patient care costs of CPR applied to patients already receiving life support in an ICU. The medical records of patients who developed cardiac arrest and underwent CPR in the ICU of a comprehensive cancer center between 1993 and 2000 were reviewed. ICU charges after the first episode of CPR were analyzed. There were 5,196 admissions to the ICU during this time; 406 (8%) of the patients underwent CPR; 67% had hematologic malignancies or had undergone hematopoietic stem cell transplantation: 256 patients (63%) died at the time of the arrest, and in 150 (37%) spontaneous circulation was restored. There were 104 patients (26%) who survived more than 24 hours but ultimately died during their hospitalization; their mean time to death was 4.3 days (95% confidence interval [CI] 2.9-5.6), and mean ICU charges were $45,877 (95% CI $24,802-$66,952). Seven patients (2%) survived to be discharged. Patients who survived after CPR and were discharged from the hospital were those who had acute ventricular dysrhythmias and were resuscitated promptly. The application of CPR to cancer patients receiving life support is costly and typically does not lead to long-term survival. Cancer patients requiring admission to an ICU should receive full supportive care short of resuscitation. Providing assurances that care will remain appropriate, aggressive, and in accordance with the patient's and family's wishes can optimize compassionate care while avoiding futile life-sustaining interventions.

Adolescent↗